The ultimate objective of this project is to discover the mechanism responsible for the elevation in blood pressure in chronic experimental one kidney, one-clip hypertension. The same mechanism may be involved in human low renin essential hypertension which includes 30% of all hypertensives and in which the cause is also unknown. The blood pressure of rabbits with this form of hypertension can be lowered by immunization with purified hog renin. Plasma from such rabbits has been collected and the antirenin antibodies removed by passage over columns of highly purified renin-Sepharose. The remaining IgG fraction was used to passively immunize and lower the blood pressure of hypertensive rabbits. This shows that in addition to antirenin, a second antibody is produced in the rabbit that is directly immunized with purified renin. Renin, in vivo, may assume a different conformation revealing new antigenic sites thus becoming a new substance - antigen M. When hog renin is used to directly immunize rabbits it is transformed into antigen M, elicits the formation of an anti-antigen M which crossreacts with the rabbits own antigen M, and lowers the blood pressure. The same antirenin free antibody preparations, used with fluorescein labeled second antibody, stained the cytoplasm of smooth muscle, and certain other cells in sections of kidney, aorta, carotid artery, and other organs from normal and hypertensive rabbits. The function of antigen M in these locations is not known but must include vasoconstriction since its neutralization lowers the blood pressure of hypertensive rabbits. A monoclonal antibody will be developed and used to purify antigen M. The product will be characterized with particular attention to discovering a relationship to renin. In vivo conversion of renin to antigen M will be demonstrated by intravenous injection of 125I-labeled renin into rabbits followed by isolation of 125I-labeled antigen M from arterial smooth muscle. Other plans include the development of a radioimmunoassay for antigen M, the determination of subcellular location of antigen M, a search for the site of conversion of renin to antigen M, and testing antigen M for direct pressor activity.